Richardson began her acting career in the theater before roles in television and film. In film, she played small parts in Prelude to a Kiss, Mo' Money, Posse, and later had major roles in Sioux City and A Low Down Dirty Shame. From 1994 to 1996 she had voice role of Elisa Maza on the animated series Gargoyles. She had many guest-starring roles in numerous television shows, such as Star Trek: Deep Space Nine, New York Undercover, The Pretender, Stargate SG-1, NYPD Blue, House, Bones, Criminal Minds, NCIS and Castle.

Richardson starred opposite Dixie Carter and Kathleen Quinlan in the CBS legal drama series, Family Law, from 1999 to 2002. She had recurring roles as Nancy Adams on Rude Awakening, and as Laura on CSI: Miami. She starred opposite Denzel Washington in the 2002 drama film Antwone Fisher. She also appeared in the 2004 horror filmAnacondas: The Hunt for the Blood Orchid and starred opposite Will Smith in 2007's post-apocalyptic film I Am Legend. She later had a leading role in the independent dramas Pastor Brown (2009) and I Will Follow (2010). She also starred in the The Sin Seer with Isaiah Washington, set for 2015 release.

From 2006 to 2012, Richardson starred as Department of Defense agent (and later head of Global Dynamics) Allison Blake in the Syfy comedy-drama series Eureka. Her second pregnancy was written into the storyline of the series. After the series' cancellation, she was cast as the lead in the Lifetime drama pilot The Secret Lives of Wives. In 2014, Richardson was cast in a recurring role on Lifetime's The Lottery as the first lady of the United States, but she lost it to Shelley Conn; She also has a role on BET's Being Mary Jane as an old friend of the lead character.